Anesthesia Management for the Patient with Chronic Decompensated Heart Failure and Low Cardiac Output Undergoing CABG with Advanced Cardiac Monitoring: A Case Report.

Introduction: Heart failure (HF) is a complex clinical syndrome caused by a structural or functional heart disorder. One of the most important challenges for anesthesiologists is the management of anesthesia in patients with severe heart failure, which has been facilitated by advanced monitoring systems. Case Presentation: The patient was a 42-year-old man with a history of hypertension (HTN) and HF with involvement of the three coronary arteries (3VD) with ejection fraction (EF) 15%. He was also a candidate for elective CABG. In addition to the insertion of arterial line in the left radial artery and the Swan-Ganz catheter in the pulmonary artery, the patient was also monitored by the Edwards Lifesciences Vigilance II for cardiac index (CI) and intravenous mixed blood oxygenation (ScvO2). Hemodynamic changes during and after surgery, as well as during inotrope infusion, were controlled, and the amount of fluid therapy was calculated by gold direct therapy (GDT) method. Conclusions: Using PA catheter with advanced monitoring and GDT-based fluid therapy guaranteed a safe anesthesia in this patient with severe heart failure and EF < 20%. Moreover, the postoperative complications and duration of ICU stays were significantly reduced.

Mapping the evolution of regional brain network efficiency and its association with cognitive abilities during the first twenty-eight months of life.

Human brain undergoes rapid growth during the first few years of life. While previous research has employed graph theory to study early brain development, it has mostly focused on the topological attributes of the whole brain. However, examining regional graph-theory features may provide unique insights into the development of cognitive abilities. Utilizing a large and longitudinal rsfMRI dataset from the UNC/UMN Baby Connectome Project, we investigated the developmental trajectories of regional efficiency and evaluated the relationships between these changes and cognitive abilities using Mullen Scales of Early Learning during the first twenty-eight months of life. Our results revealed a complex and spatiotemporally heterogeneous development pattern of regional global and local efficiency during this age period. Furthermore, we found that the trajectories of the regional global efficiency at the left temporal occipital fusiform and bilateral occipital fusiform gyri were positively associated with cognitive abilities, including visual reception, expressive language, receptive language, and early learning composite scores (P < 0.05, FDR corrected). However, these associations were weakened with age. These findings offered new insights into the regional developmental features of brain topologies and their associations with cognition and provided evidence of ongoing optimization of brain networks at both whole-brain and regional levels.

Accumulation of network redundancy marks the early stage of Alzheimer's disease.

Brain wiring redundancy counteracts aging-related cognitive decline by reserving additional communication channels as a neuroprotective mechanism. Such a mechanism plays a potentially important role in maintaining cognitive function during the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). AD is characterized by severe cognitive decline and involves a long prodromal stage of mild cognitive impairment (MCI). Since MCI subjects are at high risk of converting to AD, identifying MCI individuals is essential for early intervention. To delineate the redundancy profile during AD progression and enable better MCI diagnosis, we define a metric that reflects redundant disjoint connections between brain regions and extract redundancy features in three high-order brain networks-medial frontal, frontoparietal, and default mode networks-based on dynamic functional connectivity (dFC) captured by resting-state functional magnetic resonance imaging (rs-fMRI). We show that redundancy increases significantly from normal control (NC) to MCI individuals and decreases slightly from MCI to AD individuals. We further demonstrate that statistical features of redundancy are highly discriminative and yield state-of-the-art accuracy of up to 96.8 ± 1.0% in support vector machine (SVM) classification between NC and MCI individuals. This study provides evidence supporting the notion that redundancy serves as a crucial neuroprotective mechanism in MCI.

A comprehensive survey of permethrin resistance in human head louse populations from northwest Iran: ex vivo and molecular monitoring of knockdown resistance alleles.

BACKGROUND: Head louse infestation is an important public health problem, and expanding resistance to permethrin is a major challenge to its control. The mapping and detection of pyrethroid resistance are essential to the development of appropriate treatments and ensure the effectiveness of current measures. The aim of this study was to present the phenotypic and genotypic basis of permethrin resistance and identify knockdown resistance (kdr) mutations in head louse populations in northwestern Iran. METHODS: Adult head lice were collected from 1059 infested girls in Ardebil, East Azerbaijan, West Azerbaijan and Zanjan Provinces, northwestern Iran. The toxicity of permethrin and the possible synergistic effect of piperonyl butoxide (PBO) on this toxicity were assessed using bioassays. Fragments of voltage-sensitive sodium channels (vssc) and cytochrome b (cytb) genes were amplified and analyzed for the detection of knockdown resistance (kdr) mutations and mitochondrial groups. Moreover, genotypes of the two hot spot regions of the vssc gene were determined by melting curve analysis of amplicons. RESULTS: A total of 1450 adult head lice were collected during 2016-2021. Live lice were exposed to a dose of 1% permethrin for 12 h, and the median lethal time (LT50) and time to achieve 90% mortality (LT90) were determined to be 6 and 14.8 h, respectively. Topical application of 2 and 16 ng permethrin per louse resulted in 25% and 42.11% mortality, respectively. Pre-exposure of samples to 3% piperonyl butoxide had no synergistic effect on the effects of permethrin. Analysis of the 774-bp vssc gene fragment showed the presence of the M815I, T917I and L920F mutations, wild-type and T917I mutation, in 91.6%, 4.2% and 4.2% of samples, respectively. Investigation of the mitochondrial cytb gene demonstrated the predominance of clade B. The frequency of domain II segment 4 (S4)-S5 kdr genotypes in mitochondrial groups was identical, and heterozygotes were present in 93.5% of samples. A significant difference was detected in the frequency of domain IIS1-S3 kdr genotypes, and the frequency of resistant alleles and heterozygotes was higher in clade B than in clade A. CONCLUSIONS: The presence of kdr mutations in the vssc gene and the non-synergist effect of PBO indicate that pyrethroid target site insensitivity is the main resistance mechanism. This phenomenon and the high frequency of resistant alleles necessitate that new pediculosis management programs be developed. Further studies need to be conducted to identify all factors contributing this resistance and to develop alternative pediculicides.

Discordant immune response among treatment experienced patients infected with HIV-1: Crosstalk between MiRNAs expression and CD4+ T cells count.

BACKGROUND: One of the problems with treating HIV-infected patients with ARVs is that the treatment can reduce viral load and does not increase the number of CD4 cells (immunological discordance). There are still challenges to treating HIV-positive patients. AIM: This study aimed to investigate the expression level of 18 miRNAs involved in the proliferation and differentiation of CD4+ T cells in a target (discordant immune response) and a control (immune response) group. METHODS: In this case-control study, 18 miRNAs were selected and synthesized according to the in-silico analysis and published literatures. RNA extraction was performed from PBMC cells of 30 HIV-1 positive patients in the sample bank. The expression level of microRNAs was calculated by the relative q PCR method (2-ΔΔCt method), and data were analyzed using GraphPad Prism software version 8.0.2. RESULTS: The results of fold change calculation and statistical analysis showed that the expression levels of miR-30b (p value: 0.01, fold change: 0.23), miR-155 (p value: 0.04, fold change: 0.44), miR-181a (p value: 0.01, fold change: 0.37), and miR-190b (p value: 0.01, fold change: 0.39) had a significant decrease in the target group compared to the control group. CONCLUSION: In summary, various studies have shown that miRNAs, including miR-30b, miR-155, miR-181a, and miR-190b, are involved in the proliferation, differentiation, and development of CD4+ T cells. One reason for the lack of increase in CD4+ T cells may be the reduced expression of these miRNAs.

Bidirectional prediction of facial and bony shapes for orthognathic surgical planning.

This paper proposes a deep learning framework to encode subject-specific transformations between facial and bony shapes for orthognathic surgical planning. Our framework involves a bidirectional point-to-point convolutional network (P2P-Conv) to predict the transformations between facial and bony shapes. P2P-Conv is an extension of the state-of-the-art P2P-Net and leverages dynamic point-wise convolution (i.e., PointConv) to capture local-to-global spatial information. Data augmentation is carried out in the training of P2P-Conv with multiple point subsets from the facial and bony shapes. During inference, network outputs generated for multiple point subsets are combined into a dense transformation. Finally, non-rigid registration using the coherent point drift (CPD) algorithm is applied to generate surface meshes based on the predicted point sets. Experimental results on real-subject data demonstrate that our method substantially improves the prediction of facial and bony shapes over state-of-the-art methods.

Altered Connectedness of the Brain Chronnectome During the Progression to Alzheimer's Disease.

Graph theory has been extensively used to investigate brain network topology and its changes in disease cohorts. However, many graph theoretic analysis-based brain network studies focused on the shortest paths or, more generally, cost-efficiency. In this work, we use two new concepts, connectedness and 2-connectedness, to measure different global properties compared to the previously widely adopted ones. We apply them to unravel interesting characteristics in the brain, such as redundancy design and further conduct a time-varying brain functional network analysis for characterizing the progression of Alzheimer's disease (AD). Specifically, we define different connectedness and 2-connectedness states and evaluate their dynamics in AD and its preclinical stage, mild cognitive impairment (MCI), compared to the normal controls (NC). Results indicate that, compared to MCI and NC, brain networks of AD tend to be more frequently connected at a sparse level. For MCI, we found that their brains are more likely to be 2-connected in the minimal connected state as well indicating increasing redundancy in brain connectivity. Such a redundant design could ensure maintained connectedness of the MCI's brain network in the case that pathological damages break down any link or silenced any node, making it possible to preserve cognitive abilities. Our study suggests that the redundancy in the brain functional chronnectome could be altered in the preclinical stage of AD. The findings can be successfully replicated in a retest study and with an independent MCI dataset. Characterizing redundancy design in the brain chronnectome using connectedness and 2-connectedness analysis provides a unique viewpoint for understanding disease affected brain networks.

Alterations of dynamic redundancy of functional brain subnetworks in Alzheimer's disease and major depression disorders.

The human brain is not only efficiently but also "redundantly" connected. The redundancy design could help the brain maintain resilience to disease attacks. This paper explores subnetwork-level redundancy dynamics and the potential of such metrics in disease studies. As such, we looked into specific functional subnetworks, including those associated with high-level functions. We investigated how the subnetwork redundancy dynamics change along with Alzheimer's disease (AD) progression and with major depressive disorder (MDD), two major disorders that could share similar subnetwork alterations. We found an increased dynamic redundancy of the subcortical-cerebellum subnetwork and its connections to other high-order subnetworks in the mild cognitive impairment (MCI) and AD compared to the normal control (NC). With gained spatial specificity, we found such a redundancy index was sensitive to disease symptoms and could act as a protective mechanism to prevent the collapse of the brain network and functions. The dynamic redundancy of the medial frontal subnetwork and its connections to the frontoparietal subnetwork was also found decreased in MDD compared to NC. The spatial specificity of the redundancy dynamics changes may provide essential knowledge for a better understanding of shared neural substrates in AD and MDD.

Green synthesis of nonprecious metal-doped copper hydroxide nanoparticles for construction of a dopamine sensor.

Background: Copper oxide nanoparticles doped with nonprecious metal species (Ni and Mn) were synthesized. Method: A glassy carbon electrode (GCE) was modified by drop-casting of nanostructure suspensions, constructing Ni:Cu(OH)2/GCE, Mn:Cu(OH)2/GCE and Cu(OH)2/GCE. Results: The voltammetric oxidation of dopamine (DA) by the constructed electrodes confirmed that the electrocatalytic oxidation of DA is a reversible, pH-dependent, diffusion-controlled process; the best response was obtained by Mn:Cu(OH)2/GCE. A sensitive calibration graph (0.664 µA/µM) was produced for DA in the concentration range of 0.3-10.0 µM, with a detection limit of 79 nM using Mn:Cu(OH)2/GCE. Conclusion: The Mn:Cu(OH)2/GCE possessed an accurate response toward DA with an acceptable selectivity, stability and antifouling effect, revealing the applicability of the Mn:Cu(OH)2/GCE for DA analysis in biological samples.

Expression of mir-221, mir-29a, mir-155 and mir-146a in Peripheral Blood Mononuclear Cell (PBMC) in HIV-1 Infected Patients.

AIMS AND OBJECTIVES: In patients infected by HIV-1, some cellular biomarkers such as microRNAs have an important function in the suppression or progression of the disease. The aim of the current study is to evaluate the expression of mir-221, mir-29a, mir-155, and mir-146a in HIV-1 infected patients. METHODS: The miRNAs of 60 HIV-1 infected patients (sample group) and 20 healthy controls (normal group) were extracted from their peripheral mononuclear cells. We used TaqMan-based Real-- time PCR for evaluation of expression mir-155, mir-221, mir-29a and mir-146a by the comparative method. To evaluate differences among the data, one-way ANOVA was used. The expression of mir-155 and mir-146a in HIV-1 patients (sample group) was down-regulated in comparison with healthy controls (normal group) with a confidence value (p <0.001). In addition, in the sample group, the expression of mir-221 was downregulated compared to the normal group (p <0.001). RESULTS: There was no significant difference in expression mi-29a in the sample and control group. In the sample group, mir-221 had a low expression, and mir-29a had a high expression, respectively. According to the results of the current study and comparative studies, it seems that the microRNA has an important role in the progression or suppression of HIV-1 infection. CONCLUSION: However, the data showed that besides other cellular and viral factor, these miRNAs could be used as a biomarker. However, the miRNAs field experts are in general agreement that more investigation is needed to use miRNAs as a biomarker in HIV.

The Effects of Low HER2/neu Expression on the Clinicopathological Characteristics of Triple-Negative Breast Cancer Patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer (BC), and its diagnosis is associated with negative expression of hormone receptors and HER2/neu. It consists of 10-20% of all BCs diagnosed. METHODS AND MATERIALS: This study focuses on three groups with different pathology: group one showed complete triple-negative HER2 expression with IHC of BC; groups two and three included patients with ER-, PR-, and HER21+, and ER-, PR-, and HER22+ with a negative FISH test. These three groups were compared from the point of prognosis, which consisted of tumor size, patients' age, lymphatic, vascular and perineural invasion, organ metastasis, number of lymph nodes involvement, and the survival rate. RESULTS: A total of 459 TNBC patients were enrolled, of which 268 were placed in the HER20 group, 146 in the HER21+ group, and 45 in the HER22+ group. Distant metastasis and recurrence rate were more common in HER20 patients, but bone metastasis was more common in patients with low HER2 expression. All patients with HER20 had a smaller tumor size at the time of BC diagnosis in comparison to patients in the low HER2 expression group. Patients with HER22+ had less lymphatic and vascular invasion as well as axillary lymph nodes involvement, but larger tumor size at presentation, resulting in a lower rate of recurrence and higher overall survival. CONCLUSION: The findings revealed that patients with HER22+ had better outcome in comparison to the patients with HER20 and HER21+. Furthermore, the results showed that many patients with HER22+ expression were not basal-like and had good prognosis amongst TNBC patients.

Diversity of mitochondrial genes and predominance of Clade B in different head lice populations in the northwest of Iran.

BACKGROUND: The head louse, Pediculus humanus capitis, is the most important ectoparasite causing many health problems. Several linkages are presented for this parasite, each representing a particular geographical distribution, prevalence rate, vector competence, susceptibility to pediculicides, and infestation rate. Determining the genetic nature of these linkages is necessary to identify the population structure and also to develop and monitor control programmes against head lice. This study was designed to analyse cox1 and cytb genes and determine the mitochondrial clades in head lice populations in the northwest of Iran. METHODS: Adult head lice were collected from infested females of Ardabil, East and West Azerbaijan, and Zanjan Provinces from 2016 to 2018. Partial fragments of the mitochondrial genes cox1 and cytb were amplified by PCR and some of the amplicons were sequenced. All confirmed sequences were analysed, and the frequency of each mitochondrial clade was determined in the studied areas. RESULTS: A total of 6410 females were clinically examined, and 897 adult head lice were collected from 562 infested cases. Genomic DNA was extracted from 417 samples, and fragments of cox1 and cytb genes were amplified in 348 individuals. Analysis of the 116 sequences showed the 632-bp and 495-bp fragments for cox1 and cytb genes, respectively. The nucleotide and haplotype diversities of cytb and cox1 genes were 0.02261 and 0.589 and 0.01443 and 0.424, respectively. Sequence analysis indicated 6 haplotypes clustered in two clades, A and B. The relative prevalence of clade B was 73% for cytb and 82% for cox1 gene. Haplotypes of clade B were found in all the studied areas, while those of clade A were observed only in rural and suburban areas. CONCLUSIONS: To our knowledge, this is the first study investigated deeply the field populations of Pediculus and documented two clades in the Middle East. The considerable prevalence of pediculosis in the studied areas requires authorities' attention to establish effective control and preventive measures. Given the role of cytb in monitoring population groups, application of this marker is suggested for future epigenetic studies to evaluate the factors affecting the abundance of these clades.

Regulation of HSVtk gene by endogenous microRNA-122a in liver cell lines as suicide gene therapy.

AIM: Here, we use miR-122a that exhibits liver-specific expression for developing a post-transcriptional regulative system mediated by microRNAs. BACKGROUND: Gene therapy with adenovirus (Ad) vectors that express herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) have been suggested as a therapeutic strategy to cancer. However, Ad vectors injected into tumors are dispersed into the systemic circulation and transduce liver cells, resulting in severe hepatotoxicity. To be effective, the delivery and expression of suicide genes to cancer treatment ought to be specific to tumor cells, and avoid death of healthy cells. Researchers have demonstrated that expression of transgene could be suppressed in healthy cells with use of vectors that are reactive to microRNA regulation. METHODS: We constructed an Ad vector carrying four tandem copies of target sequences of miR-122a that were incorporated into 3'-UTR of HSVtk gene. The expression level of miR-122a was quantified in HepG2 and Huh7 cell lines. RESULTS: Quantitative RT- PCR analysis demonstrated that Huh7 cells express large amounts of miR-122a compared to HepG2 cells. The viability of Huh7 cells and HepG2 cells after infection by Ad-tk-122aT vector was 83% and 23.5%, respectively. The viability of Huh7 cells was not reduced in the presence of GCV after infection by Ad-tk-122a vector. In contrast, cytotoxicity of HSV-tk/GCV was similar in Huh7 cells and HepG2 cells by Ad-tk vector, with 35.3% and 27% viability, respectively. CONCLUSION: Inclusion of the miR-122a target sequences in the HSVtk expression cassette yielded a feasible strategy for reducing cytotoxicity of suicide gene in a liver cell line with high miR-122a expression.

Trimethyl Chitosan Improves Anti-HIV Effects of Atripla as a New Nanoformulated Drug.

BACKGROUND: Highly active antiretroviral therapy (HAART) has been commonly used for HIV treatment. Its main drawbacks like drug resistance and side effects raised researcher's interest to find new approaches for its treatment. Trimethyl chitosan is one of the drug carriers which has been introduced recently. MATERIALS AND METHODS: the conjugated atripla-trimethyl chitosan was designed and characterized by zetasizer, AFM and FTIR techniques. The drug conjugation with trimethyl chitosan and cellular uptake of nano-conjugate were determined by spectrophotometry. XTT test was used to measure the cytotoxicity. Anti-retroviral efficiency was studied by ELISA test. RESULTS: Zetasizer Results proved that the average size of nano-conjugate particles agglomeration was 493.4±24.6 nm but the size of the majority of the particles was 177.2±7.8 nm with the intensity of 87.9%. AFM technique revealed that the sizes of nano-conjugate and trimethyl chitosan were 129 nm and 59.78 nm, respectively. Zeta potential was -1.35±0.04 mv for nano-conjugate and -7.69±0.3 mv for drug. Conjugation efficiency of atripla with trimethyl chitosan was 5.27%. Measured cellular uptake with spectrophotometry for nano-conjugate was about twice of the free drug in examined concentrations (P=0.007). Compared to atripla, the nano-conjugate showed a higher inhibitory effect on HIV replication (P=0.0001). CONCLUSION: The result showed that atripla-TMC conjugate does not have a significant cytotoxicity effect. Due to the higher inhibitory effect of nano-conjugate on viral replication, it can be used in lower concentration for antiviral treatment, which resulted in reduction of drug resistance and other side effects.